Comparison of the prognostic value of AJCC cancer staging system 7th and 8th editions for differentiated thyroid cancer.

BACKGROUND: In the last American Joint Committee on Cancer/Tumor, Node, Metastasis (AJCC/TNM) 8th edition (TNM8), several changes were introduced to this risk stratification system to improve the prognosis of differentiated thyroid cancer (DTC). AIM: To validate the impact of TNM8 vs. TNM 7th edition (TNM7) in DTC in terms of predictive value in two hospitals from Buenos Aires, Argentina. METHODS: Retrospective study of DTC patients from two institutions. Reclassification from TNM7 to TNM8, disease-specific survival (DSS), and final clinical outcomes at the end of follow-up (recurrent/persistent structural disease) (median 5 years) were analyzed. The proportion of variation explained (PVE) was used to compare the predictive capability of DSS of both classification systems. RESULTS: Reclassification of 245 patients, aged (mean ± SD) 55 ± 15.36 years, 91% women, to TNM8 from TNM7 showed: 82% vs 57% stage I (SI), 10% vs 8.5% SII, 5% vs 22% SIII, 3% vs 12% SIV (p < 0.01). Forty percent of the population was downstaged with TNM8. Ten-year DSS rates for SI, SII, SIII and SIV in TNM7 were 100, 100, 100 and 74%, respectively and in TNM8: 97.6, 100, 100 and 37.5%, respectively. Out of 4 disease-specific deaths in SIV TNM7, one was subclassified to SI TNM8, corresponding to a 53-year-old patient with structural persistence. PVE for TNM8 (29%) was more than twice that of TNM7 (13%). CONCLUSION: In this Argentinian DTC patients sample, it was confirmed that the new TNM8 classification is more accurate in predicting survival attributable to cancer than its previous version.

Relevance of TSH evaluation in elderly in-patients with non-thyroidal illness.

BACKGROUND: Non-thyroidal illness (NTI) is frequent in hospitalized patients. Its recovery is characterized by a raise in TSH levels. However, the clinical significance of high TSH levels at admission in hospitalized elderly patients with NTI remains uncertain. AIM: To explore the relevance of baseline TSH evaluation in hospitalized elderly patients with NTI. METHODS: We examined the participants with NTI (n = 123) from our previous study (Sforza, 2017). NTI was defined as: low T3 (< 80 ng/dL) and normal or low total T4 in the presence of TSH values between 0.1 and 6.0 mU/L. Thyroid function tests were performed on day 1 and day 8 of the hospital stay. Positive TSH changes (+ ΔTSH) were considered when the day-8 TSH value increased more than the reference change value for TSH (+ 78%). Multiple logistic regression was used to evaluate the independent association of baseline TSH, sex, clinical comorbidities (by ACE-27) and medications with + ΔTSH. RESULTS: Out of 123 patients (77 ± 8 years, 52% female), 34 showed a + ΔTSH. These patients had a lower TSH at admission (p < 0.001) and intra-hospital mortality (p = 0.003) than the others. In multiple logistic regression, TSH > 2.11 mU/L at baseline was associated with reduced odds to show + ΔTSH [odds ratio (95 CI) 0.29 (0.11-0.75); p = 0.011] in a model adjusted by age, sex and ACE-27. DISCUSSION: Inappropriately higher TSH levels at admission in hospitalized elderly patients were associated with a reduced ability to raise their TSH levels later on. The present results confront the idea that TSH levels at admission are irrelevant in this clinical context.

Valor pronostico del hipotiroidismo en adultos mayores internados / Prognostic value of hypothyroidism in hospitalized elderly

INTRODUCCIÓN Mientras los niveles bajos de T3 han sido asociados con incremento de la mortalidad en pacientes con enfermedades no transmisibles (ENT), el impacto del hipotiroidismo manifiesto en su pronóstico es incierto. OBJETIVOS Definir las características de la función tiroidea de los pacientes adultos mayores hospitalizados y, a su vez, evaluar el papel del hipotiroidismo manifiesto en su evolución y pronóstico. MÉTODOS Se incluyó a todos los pacientes mayores de 60 años que habían sido ingresados al Servicio de Clínica Médica (n:451). Se excluyó a los pacientes ingresados a unidades de cuidados intensivos (UCI) y a otros servicios. RESULTADOS La población estudiada consistió en 243 mujeres (54%) y 208 hombres (46%) con una mediana de 77 años de edad. La causa principal de hospitalización fue respiratoria (18%), seguida de hematológica (15%). La prevalencia de antecedentes de enfermedad tiroidea fue del 17,5%. La mayoría de estos casos (96%) se debieron a hipotiroidismo anterior. Entre estos pacientes, la levotiroxina se interrumpió en el 18% de los casos en el primer día de hospitalización. Se clasificó como ENT (76%), hipotiroidismo severo (4%), hipotiroidismo subclínico (10%), hipertiroidismo subclínico (1%) y eutiroidismo (9%). Los pacientes clasificados como hipotiroidismo manifiesto eran en su mayoría añosos, requirieron pase a UCI y tuvieron mayor mortalidad comparados con los otros grupos. Los pacientes clasificados como hipotiroidismo manifiesto presentaron tasas más altas de mortalidad que los pacientes con ENT. No se observaron diferencias significativas en las tasas de mortalidad entre ENT y los pacientes con hipotiroidismo subclínico. DISCUSIÓN Los pacientes con hipotiroidismo manifiesto requirieron pase a UCI y tuvieron mayor mortalidad comparados con los otros grupos. A su vez, presentaron tasas más altas de mortalidad que los pacientes con ENT. No se observaron diferencias significativas en las tasas de mortalidad entre ENT y los pacientes con hipotiroidismo subclínico.

Hypothyroidism in hospitalized elderly patients: a sign of worse prognosis.

PURPOSE: Overt hypothyroidism has adverse clinical consequences and might worsen prognosis in critically ill elderly patients. However, the difficult interpretation of thyroid function tests (TFT) due to non-thyroidal illness (NTI) has led to discouragement of screening for thyroid dysfunction. Our aim was to determine the prevalence of TFT compatible with hypothyroidism and to study its influence on mortality among hospitalized elderly patients. METHODS: In this prospective study we consecutively included all patients ≥60 years admitted by the Internal Medicine Department to the hospital ward (n = 451) of the Cesar Milstein Hospital in Buenos Aires, Argentina. TFT were done on day 1 and 8. Thyroid function categories were defined as overt and subclinical hypothyroidism, overt and subclinical hyperthyroidism, euthyroidism and NTI. Stage of chronic kidney disease (CKD), Adult Comorbidity Evaluation (ACE)-27, and intra-hospital mortality were recorded. The association between mortality and TFT categories was studied by Cox regression. RESULTS: Out of 451 patients (77.0 ± 7.9 years, 54% females) 76% were categorized as NTI, 4% as overt hypothyroid, 10% as subclinical hypothyroid, 1% as subclinical hyperthyroid and 9% as euthyroid. Overt hypothyroid patients showed significantly higher mortality than the rest of the groups (25%, p < 0.05) while ACE-27 was similar among all of them (p = 0.658). In addition, patients within the overt hypothyroid category showed a higher mortality rate than NTI in a model adjusted by Stage 5-CKD, ACE-27, sex and age [HR 3.1 (1.14-8.41), p < 0.026]. CONCLUSION: Overt hypothyroidism during hospitalization was associated with elevated mortality. Further studies would reveal if TFT alterations compatible with hypothyroidism should be diagnosed/treated in hospitalized elderly patients.

Correlación entre osteocalcina, insulinorresistencia, insulinosensibilidad y metabolismo de la glucosa en adultos mayores con síndrome metabólico / Correlation between Osteocalcin, Insulin Resistance, Insulin Sensitivity and Carbohydrate Metabolism in an Elderly Population with Metabolic Syndrome

Introducción: Recientemente han surgido nuevas evidencias que relacionan el metabolismo óseo con el energético. La osteocalcina es una proteína de la matriz ósea no colágena, sintetizada por los osteoblastos que modula localmente la mineralización ósea, tradicionalmente usada como marcador de formación ósea. Se ha demostrado tanto en modelos "in vitro" como en animales de experimentación que la osteocalcina tiene acción hormonal. Esta proteína tiene la propiedad de regular la insulinosensibilidad, la insulinosecreción y la proliferación de las células beta pancreáticas. Objetivo: Evaluar la existencia de correlación entre los niveles de osteocalcina sérica y marcadores de insulinorresistencia (IR) e insulinosensibilidad en una población de adultos mayores con síndrome metabólico. Material y métodos: En nuestro estudio prospectivo se incluyeron 88 pacientes (68 % mujeres, 32 % hombres, media de edad 73 ± 6 y 74 ± 6 años respectivamente) que concurrieron a los consultorios externos del servicio de Endocrinología y Metabolismo del hospital Dr. César Milstein. Todos cumplían con los criterios diagnósticos de síndrome metabólico del año 2009 de la Federación Internacional de Diabetes (IDF). Se midieron: osteocalcina sérica, hemoglobina glicosilada (HbA1c), HDL y triglicéridos (TG). Se calcularon QUICKI (Quantitative Insulin Sensivity Check Index) y el índice TG/HDL. Resultados: Los niveles de osteocalcina sérica se asociaron positivamente con HDL (r = 0,213, p = 0,05) y QUICKI (r = 0,212, p = 0,05) e inversamente con TG (r = -0,218, p < 0,05), con el índice TG/HDL (r = -0,217, p < 0,05) y con HbA1c (r = -0,253, p < 0,05). Conclusiones: Nuestro estudio mostró que en adultos mayores con sindrome metabólico, los niveles de osteocalcina reducidos se asociaron con un aumento en los índices de insulinorresistencia, una disminución de los de insulinosensibilidad y un peor control metabólico. Rev Argent Endocrinol Metab 52:8-13, 2015 Los autores no poseen conflictos de interés.

Introduction: In recent years there has been increasing evidence about the relationship between bone and energy metabolism. Osteocalcin is a non-collagenous bone matrix protein synthesized by osteoblasts that locally modulates bone mineralization and is traditionally used as a bone formation marker. Osteocalcin has been shown to have hormonal actions both in in vitro models and in experimental animals. This hormone has the property of regulating insulin secretion and insulin sensitivity as well as beta pancreatic cell proliferation. Aim: To evaluate the existence of correlation between serum osteocalcin levels, insulin resistance and insulin sensitivity markers in an elderly population with metabolic syndrome. Material and methods: Eighty-eight elderly patients were included in our prospective study (68 % women, mean age 73 ± 6 ; 32 % men, mean age 74 ± 6). They attended the outpatient Endocrinology and Metabo­lism service at Dr. César Milstein Hospital and met the International Diabetes Federation (IDF) criteria of metabolic syndrome. Serum Osteocalcin, Glycated haemoglobin (HbA1c), HDL and Triglycerides (TG) were measured. QUICKI and TG/HDL index were calculated. Results: Serum osteocalcin levels were positively associated with HDL (r = 0.213, p = 0.05) and QUICKI (r = 0.212, p = 0.05), and inversely associated with TG (r = -0.218, p < 0.05), TG/HDL index (r = -0.217, p < 0.05) and HbA1c (r = -0.253, p < 0.05). Conclusions: Our study showed that in elderly patients with metabolic syndrome, reduced osteocalcin levels were associated with increased insulin sensitivity, decreased insulin resistance indexes and impaired metabolic control. Rev Argent Endocrinol Metab 52:8-13, 2015 No financial conflicts of interest exist.

Análisis de características clínicas y ecográficas de nódulos tiroideos con citología Bethesda III y su evolución / Analysis of Clinical and Ultrasound Features of Thyroid Nodules With Bethesda III Cytology and their Evolution

Introducción: Desde la implementación de la clasificación citológica de los nódulos tiroideos por el sistema Bethesda en 6 categorías, el grupo Bethesda III (BIII) es el que genera más controversias en cuanto a la conducta de seguimiento. Según la literatura corresponden a esta categoría entre el 4 y 20 % de los nódulos punzados y conllevan un riesgo de malignidad del 5-15 %. Objetivo: Determinar características clínicas y ecográficas de los nódulos tiroideos clasificados como BIII en nuestra población y analizar su evolución en el tiempo. Materiales y Métodos: Estudio descriptivo de todos los pacientes enviados a PAAF bajo guía ecográfica que resultaron BIII, entre febrero 2011 y diciembre 2013. Se describieron las características clínicas y ecográficas de dichos nódulos y su evolución. La mediana de seguimiento fue 24 meses (rango: 2 a 35 meses). Resultados: Fueron punzados 945 nódulos de 784 pacientes. Se clasificaron como BIII 85 nódulos (8,99 %) de 72 pacientes (69 mujeres y 3 varones), con una media de edad de 71,1 ±7,1 años. La mediana del diáme­tro mayor de los nódulos fue 18 mm (9 a 54 mm). El 76,1 % de los nódulos fueron sólidos, el 22,5 % mixtos y en 1 caso espongiforme. Según el patrón ecográfico: 36,7 % eran hipoecoicos, 54,4 % isoecoicos y 8,9 % hiperecoicos. El 8,33 % presentó microcalcificaciones y el 9,9 % márgenes irregulares. El 39,43 % presentó vascularización periférica, 4,23 % central y 56,34 % mixta. Evolución: De los 72 pacientes, 9 (12,1 %) se perdieron en el seguimiento, a 56 (77,8 %) se los siguió clínica y ecográficamente, y en 7 pacientes (9,7 %) se tomó conducta quirúrgica basándose en criterios clínicos y ecográficos sospechosos de malignidad, o por antecedentes familiares positivos, resultando 3 con carcinoma papilar (CP), y 4 con patología benigna. Durante el seguimiento, Fueron repunzados 40 nódulos de 35 pacientes (48,6 %) que resultaron: 2 BI, 23 BII, 14 BIII y 1 BV. De los 14 nódulos con segunda punción BIII, se operaron 7, 1 CP y 6 patología benigna. El nódulo BV resultó un CP a su cirugía. En total, fueron operados 16 pacientes con BIII (22,2 %) (7 de inicio y 8 luego de la segunda PAAF y 1 en el seguimiento clínico ecográfico), de los cuales 5 (31,25 %) resultaron CP y 11 (68,75 %) patología tiroidea benigna. Conclusión: Si bien para los nódulos tiroideos con categoría BIII se recomienda generalmente una repunción, en nuestra experiencia el hallazgo de características clínicas y ecográficas sospechosas de malignidad y/o antecedentes familiares de cáncer de tiroides permitiría en algunos pacientes optar por la cirugía tiroidea desde el inicio. Rev Argent Endocrinol Metab 52:14-21, 2015 Los autores declaran no poseer conflictos de interés.

Background: Since the implementation of the Bethesda System for cytology classification of thyroid nodules into 6 categories, the Bethesda III group (B III) has been the most controversial as regards follow-up management. Reported data shows that about 4 to 20 % of all biopsied nodules belong to this category, with the risk of malignancy being 5 to 15 %. Objective: To determine clinical and sonographic features of thyroid nodules classified as BIII in our population and analyze their evolution over time. Methods: We determined the clinical and ultrasonographic (US) features of all patients who had undergone fine needle aspiration biopsy (FNAB) in 2011-2013 at our Institution for Retirees and Pensioners. Descriptive study of all patients with nodules classified as BIII with a median follow-up time of 24 months (2 to 35 months). Results: Out of 945 nodules from 784 patients biopsied (age, mean ± SD:71.1±7.1 years), 85 (8.99 %) were classified as BIII. Six patients had received neck radiation, and 5 reported family history of thyroid cancer. The median (range) largest diameter of nodules was 18 mm (9-54 mm). Fifty-four nodules (76.1 %) were solid, 16 (22.5 %) mixed, and 1 spongiform. Based on echogenicity, 36.7 % were hypoechoic, 54.4 % isoechoic and 8.9 % hyperechoic. Twenty-two nodules (25.88 %) were taller than wider, 8.33 % had microcalcifications and 9.9 % had irregular margins. At Doppler evaluation, 39.43 % of nodules had peripheral vascularity, 4.23 % showed central vascularity and 56.34 % had mixed vascularity. In 7 out of 72 patients with BIII classification, surgery was indicated at the start based on suspicious clinical and US findings for malignancy, or family history of thyroid cancer. Out of these 7 patients, 3 were found to have papillary carcinoma (PTC), 1 follicular adenoma (FA), 1 colloid goiter (CG), 1 adenomatous nodule (AN) and 1 chronic lymphocytic thyroiditis (CLT). As regards the follow-up and evolution of the rest of the group, 9 were lost, 21 remained in observation and 35 (48.6 %) with 40 nodules underwent a second FNAB, with the following results: 2 BI, 23 BII, 14 BIII and 1 BV. Out of 14 nodules confirmed as BIII on repeat FNAB, 7 were operated on, resulting in: 2 CLT, 3 CG, 1 FA and 1 PTC. The BV nodule proved to be PTC. A total of 16 patients with BIII nodules underwent surgery (7 initially, 8 after a second FNAB, and 1 during clinical and US follow-up) and 5 (31.25 %) were PTC while 11 (68.75 %) were benign. Conclusion: Even though BIII thyroid nodules generally require a second FNAB, in our experience clinical and US findings suspicious for malignancy, or family history of thyroid cancer could allow some patients to be offered surgery at initial presentation. Rev Argent Endocrinol Metab 52:14-21, 2015 No financial conflicts of interest exist.

Correlación entre osteocalcina, insulinorresistencia, insulinosensibilidad y metabolismo de la glucosa en adultos mayores con síndrome metabólico / Correlation between Osteocalcin, Insulin Resistance, Insulin Sensitivity and Carbohydrate Metabolism in an Elderly Population with Metabolic Syndrome

Introducción: Recientemente han surgido nuevas evidencias que relacionan el metabolismo óseo con el energético. La osteocalcina es una proteína de la matriz ósea no colágena, sintetizada por los osteoblastos que modula localmente la mineralización ósea, tradicionalmente usada como marcador de formación ósea. Se ha demostrado tanto en modelos "in vitro" como en animales de experimentación que la osteocalcina tiene acción hormonal. Esta proteína tiene la propiedad de regular la insulinosensibilidad, la insulinosecreción y la proliferación de las células beta pancreáticas. Objetivo: Evaluar la existencia de correlación entre los niveles de osteocalcina sérica y marcadores de insulinorresistencia (IR) e insulinosensibilidad en una población de adultos mayores con síndrome metabólico. Material y métodos: En nuestro estudio prospectivo se incluyeron 88 pacientes (68 % mujeres, 32 % hombres, media de edad 73 ± 6 y 74 ± 6 años respectivamente) que concurrieron a los consultorios externos del servicio de Endocrinología y Metabolismo del hospital Dr. César Milstein. Todos cumplían con los criterios diagnósticos de síndrome metabólico del año 2009 de la Federación Internacional de Diabetes (IDF). Se midieron: osteocalcina sérica, hemoglobina glicosilada (HbA1c), HDL y triglicéridos (TG). Se calcularon QUICKI (Quantitative Insulin Sensivity Check Index) y el índice TG/HDL. Resultados: Los niveles de osteocalcina sérica se asociaron positivamente con HDL (r = 0,213, p = 0,05) y QUICKI (r = 0,212, p = 0,05) e inversamente con TG (r = -0,218, p < 0,05), con el índice TG/HDL (r = -0,217, p < 0,05) y con HbA1c (r = -0,253, p < 0,05). Conclusiones: Nuestro estudio mostró que en adultos mayores con sindrome metabólico, los niveles de osteocalcina reducidos se asociaron con un aumento en los índices de insulinorresistencia, una disminución de los de insulinosensibilidad y un peor control metabólico. Rev Argent Endocrinol Metab 52:8-13, 2015 Los autores no poseen conflictos de interés.(AU)

Introduction: In recent years there has been increasing evidence about the relationship between bone and energy metabolism. Osteocalcin is a non-collagenous bone matrix protein synthesized by osteoblasts that locally modulates bone mineralization and is traditionally used as a bone formation marker. Osteocalcin has been shown to have hormonal actions both in in vitro models and in experimental animals. This hormone has the property of regulating insulin secretion and insulin sensitivity as well as beta pancreatic cell proliferation. Aim: To evaluate the existence of correlation between serum osteocalcin levels, insulin resistance and insulin sensitivity markers in an elderly population with metabolic syndrome. Material and methods: Eighty-eight elderly patients were included in our prospective study (68 % women, mean age 73 ± 6 ; 32 % men, mean age 74 ± 6). They attended the outpatient Endocrinology and Metabo¡lism service at Dr. César Milstein Hospital and met the International Diabetes Federation (IDF) criteria of metabolic syndrome. Serum Osteocalcin, Glycated haemoglobin (HbA1c), HDL and Triglycerides (TG) were measured. QUICKI and TG/HDL index were calculated. Results: Serum osteocalcin levels were positively associated with HDL (r = 0.213, p = 0.05) and QUICKI (r = 0.212, p = 0.05), and inversely associated with TG (r = -0.218, p < 0.05), TG/HDL index (r = -0.217, p < 0.05) and HbA1c (r = -0.253, p < 0.05). Conclusions: Our study showed that in elderly patients with metabolic syndrome, reduced osteocalcin levels were associated with increased insulin sensitivity, decreased insulin resistance indexes and impaired metabolic control. Rev Argent Endocrinol Metab 52:8-13, 2015 No financial conflicts of interest exist.(AU)

Análisis de características clínicas y ecográficas de nódulos tiroideos con citología Bethesda III y su evolución / Analysis of Clinical and Ultrasound Features of Thyroid Nodules With Bethesda III Cytology and their Evolution

Introducción: Desde la implementación de la clasificación citológica de los nódulos tiroideos por el sistema Bethesda en 6 categorías, el grupo Bethesda III (BIII) es el que genera más controversias en cuanto a la conducta de seguimiento. Según la literatura corresponden a esta categoría entre el 4 y 20 % de los nódulos punzados y conllevan un riesgo de malignidad del 5-15 %. Objetivo: Determinar características clínicas y ecográficas de los nódulos tiroideos clasificados como BIII en nuestra población y analizar su evolución en el tiempo. Materiales y Métodos: Estudio descriptivo de todos los pacientes enviados a PAAF bajo guía ecográfica que resultaron BIII, entre febrero 2011 y diciembre 2013. Se describieron las características clínicas y ecográficas de dichos nódulos y su evolución. La mediana de seguimiento fue 24 meses (rango: 2 a 35 meses). Resultados: Fueron punzados 945 nódulos de 784 pacientes. Se clasificaron como BIII 85 nódulos (8,99 %) de 72 pacientes (69 mujeres y 3 varones), con una media de edad de 71,1 ±7,1 años. La mediana del diáme¡tro mayor de los nódulos fue 18 mm (9 a 54 mm). El 76,1 % de los nódulos fueron sólidos, el 22,5 % mixtos y en 1 caso espongiforme. Según el patrón ecográfico: 36,7 % eran hipoecoicos, 54,4 % isoecoicos y 8,9 % hiperecoicos. El 8,33 % presentó microcalcificaciones y el 9,9 % márgenes irregulares. El 39,43 % presentó vascularización periférica, 4,23 % central y 56,34 % mixta. Evolución: De los 72 pacientes, 9 (12,1 %) se perdieron en el seguimiento, a 56 (77,8 %) se los siguió clínica y ecográficamente, y en 7 pacientes (9,7 %) se tomó conducta quirúrgica basándose en criterios clínicos y ecográficos sospechosos de malignidad, o por antecedentes familiares positivos, resultando 3 con carcinoma papilar (CP), y 4 con patología benigna. Durante el seguimiento, Fueron repunzados 40 nódulos de 35 pacientes (48,6 %) que resultaron: 2 BI, 23 BII, 14 BIII y 1 BV. De los 14 nódulos con segunda punción BIII, se operaron 7, 1 CP y 6 patología benigna. El nódulo BV resultó un CP a su cirugía. En total, fueron operados 16 pacientes con BIII (22,2 %) (7 de inicio y 8 luego de la segunda PAAF y 1 en el seguimiento clínico ecográfico), de los cuales 5 (31,25 %) resultaron CP y 11 (68,75 %) patología tiroidea benigna. Conclusión: Si bien para los nódulos tiroideos con categoría BIII se recomienda generalmente una repunción, en nuestra experiencia el hallazgo de características clínicas y ecográficas sospechosas de malignidad y/o antecedentes familiares de cáncer de tiroides permitiría en algunos pacientes optar por la cirugía tiroidea desde el inicio. Rev Argent Endocrinol Metab 52:14-21, 2015 Los autores declaran no poseer conflictos de interés.(AU)

Background: Since the implementation of the Bethesda System for cytology classification of thyroid nodules into 6 categories, the Bethesda III group (B III) has been the most controversial as regards follow-up management. Reported data shows that about 4 to 20 % of all biopsied nodules belong to this category, with the risk of malignancy being 5 to 15 %. Objective: To determine clinical and sonographic features of thyroid nodules classified as BIII in our population and analyze their evolution over time. Methods: We determined the clinical and ultrasonographic (US) features of all patients who had undergone fine needle aspiration biopsy (FNAB) in 2011-2013 at our Institution for Retirees and Pensioners. Descriptive study of all patients with nodules classified as BIII with a median follow-up time of 24 months (2 to 35 months). Results: Out of 945 nodules from 784 patients biopsied (age, mean ± SD:71.1±7.1 years), 85 (8.99 %) were classified as BIII. Six patients had received neck radiation, and 5 reported family history of thyroid cancer. The median (range) largest diameter of nodules was 18 mm (9-54 mm). Fifty-four nodules (76.1 %) were solid, 16 (22.5 %) mixed, and 1 spongiform. Based on echogenicity, 36.7 % were hypoechoic, 54.4 % isoechoic and 8.9 % hyperechoic. Twenty-two nodules (25.88 %) were taller than wider, 8.33 % had microcalcifications and 9.9 % had irregular margins. At Doppler evaluation, 39.43 % of nodules had peripheral vascularity, 4.23 % showed central vascularity and 56.34 % had mixed vascularity. In 7 out of 72 patients with BIII classification, surgery was indicated at the start based on suspicious clinical and US findings for malignancy, or family history of thyroid cancer. Out of these 7 patients, 3 were found to have papillary carcinoma (PTC), 1 follicular adenoma (FA), 1 colloid goiter (CG), 1 adenomatous nodule (AN) and 1 chronic lymphocytic thyroiditis (CLT). As regards the follow-up and evolution of the rest of the group, 9 were lost, 21 remained in observation and 35 (48.6 %) with 40 nodules underwent a second FNAB, with the following results: 2 BI, 23 BII, 14 BIII and 1 BV. Out of 14 nodules confirmed as BIII on repeat FNAB, 7 were operated on, resulting in: 2 CLT, 3 CG, 1 FA and 1 PTC. The BV nodule proved to be PTC. A total of 16 patients with BIII nodules underwent surgery (7 initially, 8 after a second FNAB, and 1 during clinical and US follow-up) and 5 (31.25 %) were PTC while 11 (68.75 %) were benign. Conclusion: Even though BIII thyroid nodules generally require a second FNAB, in our experience clinical and US findings suspicious for malignancy, or family history of thyroid cancer could allow some patients to be offered surgery at initial presentation. Rev Argent Endocrinol Metab 52:14-21, 2015 No financial conflicts of interest exist.(AU)

Particularidades del síndrome metabólico en una subpoblación de adultos mayores / Particularities of metabolic syndrome in an elderly subpopulation

Introducción: El síndrome metabólico (SM) se define por un conjunto de alteraciones clínicas que aumentan el riesgo de enfermedad cardiovascular. Diferentes organizaciones internacionales de salud han ajustado progresivamente los criterios que definen al SM, con el consiguiente aumento del diagnóstico del mismo. Sin embargo, ninguno de los parámetros considerados se han adaptado a la edad ni se han tomado en cuenta las modificaciones antropométricas y metabólicas características del envejecimiento. Objetivo: Caracterizar al SM en una población de adultos mayores y evaluar si existen diferencias de género. Materiales y métodos: Se realizó un estudio prospectivo en pacientes que consultaron al Servicio de Endocrinología de la U. A. Dr. César Milstein. El 68,8 % fueron mujeres y la edad de la población fue 73 ± 6 años. Para el diagnóstico de SM se utilizaron los criterios del Joint Interim Statement de 2009. Recabamos información sobre antecedentes, medicación y se realizaron análisis de laboratorio. Se midió índice cintura/talla (ICT). Se calculó media ± desvío estándar (DS) y proporciones. Para establecer comparaciones entre varones y mujeres se utilizó Test de Student y test de Chi2. Resultados: En una muestra de 77 pacientes, 42,9 % cumplió con 3 componentes de SM, 33,8 % con 4 y 23,4 % con 5, con distribución similar en hombres y mujeres. Según el índice de masa corporal (IMC), 32,5 % de la población presentó sobrepeso; 35 % obesidad grado I; 22 % grado II y 9 % grado III. Al evaluar el perímetro de cintura (PC), el 98,7 % superó los puntos de corte. El índice cintura/ talla superó el valor normal en ambos sexos, siendo significativamente superior en las mujeres (p: 0,003). Conclusiones: En la población de adultos mayores que se estudió no se observó diferencia entre ambos sexos en el número de componentes diagnósticos de SM. En cuanto al perímetro de cintura, el valor fue similar en ambos sexos, lo que podría llevar a revisar el valor de corte del mismo en este grupo etario. El ICT estuvo aumentado en toda la población y por ser un subrogante de riesgo cardiovascular, sería otro parámetro a tener en cuenta al momento del diagnóstico de SM. Rev Argent Endocrinol Metab 51:130-135, 2014 Los autores no poseen conflictos de interés.

Introduction: The metabolic syndrome (MS) denotes an association of abnormalities that increase the risk of cardiovascular disease. With the intention of decreasing this risk, international organizations have dropped the normal range for various parameters, with a consequent increase in the diagnosis of MS. Although the changes related to age are well documented, none of these parameters has been age-adapted. Aims: to characterize MS in the elderly population and to establish possible gender differences. Materials and methods: We performed a prospective study in patients who presented at the Department of Endocrinology of the Healthcare Unit Dr. Cesar Milstein. Of the total population, 68.8 % were women and the average age was 73 ± 6 years. For the diagnosis of MS, we used the 2009 Joint Interim Statement diagnostic criteria. Information was collected on previous history and medication, and laboratory analyses were performed. The waist / height ratio was also measured. Mean ± standard deviation (SD) and proportions were calculated. For comparisons between men and women, the Student test and Chi-squared test were used. Results: Of the total population, 42.9 % fulfilled 3 criteria for MS, 33.8 % fulfilled 4 criteria and 23.4 % fulfilled 5, with similar distribution in men and women. According to body mass index (BMI), 32.5 % of the population had overweight, 35 % were grade I obese, 22 % were grade II and 9 % were grade III. As regards waist circumference, 98.7 % of the total population exceeded the established cutoffs. The waist/ height ratio exceeded normal values in both genders, being significantly higher in women (p = 0.003). Conclusions: In the elderly, there are no gender differences in the number of components of MS. As for waist circumference, values were similar in both men and women. This finding could lead to redefine the cutoff value in aged woman. The waist / height ratio, a surrogate marker of cardiovascular disease, was ...

Carcinoma medular de tiroides: estudio multicéntrico. Presentación y evolución en 219 pacientes / Medullary Thyroid Carcinoma: Clinical Presentation and Outcome in 219 Patients

Ante la baja frecuencia del carcinoma medular de tiroides (CMT), en el Departamento de Tiroides de SAEM nos propusimos realizar un estudio de cohorte, observacional, retrospectivo y multicéntrico. Se incluyeron 219 pacientes con diagnóstico histológico de CMT. El 65 % fueron mujeres, la edad promedio fue de 39 ± 20 años (1 a 84 años); 44-% de los casos fueron familiares. Las formas de presentación más frecuentes fueron nódulo tiroideo (58 %) y pesquisa genética por antecedente familiar (22 %). Si bien la citología tiroidea fue diagnóstica de CMT en el 39 % de los casos, fue determinante de indicación quirúrgica en el 79 %. En el 47 % de los pacientes el diagnóstico de CMT se obtuvo previamente al tratamiento quirúrgico inicial por punción aspiración con aguja fina (PAAF), estudio genético o nivel de calcitonina (CT)). El 65 % se presentó en estadios avanzados (TNM III y IV). El estudio del protoncogen RET se realizó en 162 pacientes (74 %). En el 49 % se observó mutación siendo la más frecuente (76 %) en el codón 634. La forma hereditaria más frecuentemente observada fue el síndrome de neoplasia endocrina múltiple (NEM) 2A (57 % de los casos familiares), seguida por carcinoma medular familiar (25 %) y NEM 2B (13 %). Los casos familiares tuvieron menor edad al diagnóstico y mayor frecuencia de diagnóstico prequirúrgico. Los casos índice tuvieron mayor edad al momento del diagnóstico, mayores niveles de antígeno carcinoembrionario (CEA) y CT prequirúrgicos, mayor proporción de estadios III y IV y mayor porcentaje de evidencia de enfermedad al momento de la última consulta que aquellos detectados por pesquisa. En 143 pacientes (65 %) se obtuvieron registros completos de seguimiento en los que se analizaron los factores relacionados con la evolución. La mediana de seguimiento fue de 44 meses: fallecieron 21 pacientes (14,6 %) y 122 (86 %) viven; 76 de estos (54 %) se encuentran libres de enfermedad. El grupo con evidencia de enfermedad se presentó en estadios más avanzados. Resultaron factores de mayor riesgo para evidencia de enfermedad: sexo masculino, CMT esporádico, niveles elevados de CT prequirúrgicos, estadio IV y presencia de metástasis. Los niveles de CT posquirúrgicos fueron menores en aquellos pacientes que en la evolución final no presentaron evidencia de enfermedad. El principal factor pronóstico de la evolución de los pacientes con CMT fue el estadio de presentación, determinando la importancia del diagnóstico precoz con el fin de poder implementar un tratamiento quirúrgico curativo en estadios menos avanzados.

Due to the low frequency of medullary thyroid cancer (MTC), an observational, cohort, retrospective multicenter study was conducted at the Thyroid Department of the Endocrine and Metabolism Argentine Society (SAEM). We included 219 patients with histologically proven MTC, with a mean age of 39 ± 20 yr (range 1-84 years). Sixty five percent were women and 44% were familial cases. The most common presentations were thyroid nodule (58 %) and genetic screening due to family history (22 %). In 39 % of patients, diagnosis of MTC was made by fine needle aspiration, but cytology led to surgery in 79 %. In 47 % of patients, MTC was diagnosed by cytology, calcitonin (CT) levels or genetic studies prior to initial surgery. Sixty five percent of patients had advanced stages of the disease (TNM III or IV) at diagnosis. Proto-oncogene RET was studied in 162 patients (74 %). In 49% a mutation was reported, most frequently in codon 634 (76 %). Regarding hereditary forms of MTC, MEN 2A was the most frequent (57%), followed by familial MTC in 25 % and MEN 2B in 13 % of cases. Familial cases were younger subjects and had more frequently a pre-surgery diagnosis. Index cases were older, with higher CEA and CT levels, presented in more advanced stages and had more frequently evidence of disease at final assessment than patients who were diagnosed by genetic screening. Follow-up records of 143 patients were analyzed (65%); median time was 44 months; 21 patients died (14.6 %) and 122 survived (86 %), 76 showed no evidence of disease (NED) (54 %). High risk factors for evidence of disease at the final evaluation were: male gender, sporadic MTC, higher CT pre-surgery levels, stage IV and metastasis. Post surgery CT levels were lower in patients with NED. Stage at initial diagnosis was the main prognostic factor in patients with MTC, determining the importance of early detection for performing curative surgery in less advanced stages.

Carcinoma medular de tiroides: estudio multicéntrico. Presentación y evolución en 219 pacientes / Medullary Thyroid Carcinoma: Clinical Presentation and Outcome in 219 Patients

Ante la baja frecuencia del carcinoma medular de tiroides (CMT), en el Departamento de Tiroides de SAEM nos propusimos realizar un estudio de cohorte, observacional, retrospectivo y multicéntrico. Se incluyeron 219 pacientes con diagnóstico histológico de CMT. El 65 % fueron mujeres, la edad promedio fue de 39 ± 20 años (1 a 84 años); 44-% de los casos fueron familiares. Las formas de presentación más frecuentes fueron nódulo tiroideo (58 %) y pesquisa genética por antecedente familiar (22 %). Si bien la citología tiroidea fue diagnóstica de CMT en el 39 % de los casos, fue determinante de indicación quirúrgica en el 79 %. En el 47 % de los pacientes el diagnóstico de CMT se obtuvo previamente al tratamiento quirúrgico inicial por punción aspiración con aguja fina (PAAF), estudio genético o nivel de calcitonina (CT)). El 65 % se presentó en estadios avanzados (TNM III y IV). El estudio del protoncogen RET se realizó en 162 pacientes (74 %). En el 49 % se observó mutación siendo la más frecuente (76 %) en el codón 634. La forma hereditaria más frecuentemente observada fue el síndrome de neoplasia endocrina múltiple (NEM) 2A (57 % de los casos familiares), seguida por carcinoma medular familiar (25 %) y NEM 2B (13 %). Los casos familiares tuvieron menor edad al diagnóstico y mayor frecuencia de diagnóstico prequirúrgico. Los casos índice tuvieron mayor edad al momento del diagnóstico, mayores niveles de antígeno carcinoembrionario (CEA) y CT prequirúrgicos, mayor proporción de estadios III y IV y mayor porcentaje de evidencia de enfermedad al momento de la última consulta que aquellos detectados por pesquisa. En 143 pacientes (65 %) se obtuvieron registros completos de seguimiento en los que se analizaron los factores relacionados con la evolución. La mediana de seguimiento fue de 44 meses: fallecieron 21 pacientes (14,6 %) y 122 (86 %) viven; 76 de estos (54 %) se encuentran libres de enfermedad. El grupo con evidencia de enfermedad se presentó en estadios más avanzados. Resultaron factores de mayor riesgo para evidencia de enfermedad: sexo masculino, CMT esporádico, niveles elevados de CT prequirúrgicos, estadio IV y presencia de metástasis. Los niveles de CT posquirúrgicos fueron menores en aquellos pacientes que en la evolución final no presentaron evidencia de enfermedad. El principal factor pronóstico de la evolución de los pacientes con CMT fue el estadio de presentación, determinando la importancia del diagnóstico precoz con el fin de poder implementar un tratamiento quirúrgico curativo en estadios menos avanzados.(AU)

Due to the low frequency of medullary thyroid cancer (MTC), an observational, cohort, retrospective multicenter study was conducted at the Thyroid Department of the Endocrine and Metabolism Argentine Society (SAEM). We included 219 patients with histologically proven MTC, with a mean age of 39 ± 20 yr (range 1-84 years). Sixty five percent were women and 44% were familial cases. The most common presentations were thyroid nodule (58 %) and genetic screening due to family history (22 %). In 39 % of patients, diagnosis of MTC was made by fine needle aspiration, but cytology led to surgery in 79 %. In 47 % of patients, MTC was diagnosed by cytology, calcitonin (CT) levels or genetic studies prior to initial surgery. Sixty five percent of patients had advanced stages of the disease (TNM III or IV) at diagnosis. Proto-oncogene RET was studied in 162 patients (74 %). In 49% a mutation was reported, most frequently in codon 634 (76 %). Regarding hereditary forms of MTC, MEN 2A was the most frequent (57%), followed by familial MTC in 25 % and MEN 2B in 13 % of cases. Familial cases were younger subjects and had more frequently a pre-surgery diagnosis. Index cases were older, with higher CEA and CT levels, presented in more advanced stages and had more frequently evidence of disease at final assessment than patients who were diagnosed by genetic screening. Follow-up records of 143 patients were analyzed (65%); median time was 44 months; 21 patients died (14.6 %) and 122 survived (86 %), 76 showed no evidence of disease (NED) (54 %). High risk factors for evidence of disease at the final evaluation were: male gender, sporadic MTC, higher CT pre-surgery levels, stage IV and metastasis. Post surgery CT levels were lower in patients with NED. Stage at initial diagnosis was the main prognostic factor in patients with MTC, determining the importance of early detection for performing curative surgery in less advanced stages.(AU)

Programa nacional de bocio nodular (PRONBONO): Estudio multicéntrico de bocio nodular único palpable / National Program for Nodular Goiter (PRONBONO): Multicenter study of single palpable thyroid nodules

Introducción: La presencia de nódulos tiroideos palpables en la población general, es uno de los signos clínicos tiroideos más frecuentes en la práctica diaria. Objetivos: 1) establecer la prevalencia de las distintas patologías en bocio nodular único palpable y analizar sus características y su relación con los resultados citológicos. 2) analizar la existencia de diferencias regionales en Argentina. Pacientes y Métodos: Estudio prospectivo de 739 pacientes con bocio nodular único palpable evaluados entre el 1/1/2000 y el 31/12/2001 en Centros de Buenos Aires, Bahía Blanca, Mendoza y La Pampa. Se recabaron datos de examen clínico, ecografía tiroidea, TSH, ATPO y citología por punción con aguja fina. (PAAF). Fue utilizado para el análisis estadístico Correlación de Pearson, X2 y Test de Fisher. Resultados: la edad (X ± DS) fue 46,3 ± 14 años, 93,1 % eran de sexo femenino. El 1,6 % tenía historia de radiación en cuello y el 29,9 % antecedentes familiares de patología tiroidea. Hallazgos clínicos: disfagia en el 7,9 %, disfonía 3,5 %, crecimiento nodular en los últimos 6 meses 19,2 %, consistencia dura el 24,7 %, fijeza a estructuras adyacentes 1,5 % y adenopatías en el 3 %. Hallazgos bioquímicos: TSH normal en el 81,2 % y ATPO positivos en el 30,3 % de los casos. Características Ecográficas: nódulos sólidos: 53,1 %, hipoecoicos: 63,8 %, microcalcificaciones 10,3 %, halo incompleto: 15 %, multinodular: 30,5 %, tiroides heterogénea: 60,2 % y adenopatías: 3,8 %. Hallazgos citológicos: En el 86,8 % de los casos fue necesario solo una punción para llegar al diagnóstico. Insatisfactorio (excluyendo quiste): 3,2 %: benignos: 77,3 %; sospechosos: 12,6 % y cáncer: 7 % (42 papilar, 2 medular y 3 sin especificar). Una correlación significativa (p<0,02) fue observada entre citología maligna y crecimiento rápido, dureza, fijeza a estructuras vecinas, nódulo sólido, halo incompleto y adenopatías aunque estos parámetros son más frecuentes en números absolutos en nódulos benignos. La mayoría de las cirugías fueron indicadas en base al hallazgo citológico. El diagnóstico histológico de los 96 pacientes que fueron operados mostró 51 carcinomas, de los cuales solo dos tenían citología benigna y 31 adenomas. Conclusión: Los nódulos palpables únicos fueron más frecuentes en mujeres eutiroideas en la edad media de la vida. Un tercio tenía historia familiar de patología tiroidea, similar al porcentaje hallado de ATPO positivos. Por ecografía los nódulos fueron predominantemente sólidos, hipoecoicos, únicos con resto de la glándula tiroides heterogénea. La PAAF fue predominantemente benigna. El crecimiento rápido, la dureza, la fijeza a estructuras adyacentes, el halo incompleto y la presencia de adenopatías fueron relacionados con malignidad, pero la benignidad fue más frecuente. En la mayoría de los pacientes la cirugía fue recomendada por los hallazgos citológicos. Nuestros resultados son similares a los reportados en otras áreas geográficas.

Introduction: the presence of palpable thyroid nodules in the general population is one of the most common clinical signs of thyroid disease in daily practice. Objectives: 1) To assess the prevalence of pathologies, clinical and cytological findings of single palpable thyroid nodules (SPTN) in Argentina. 2) Analyze the regional differences in Argentina. Methods: Prospective study of 739 patients with STPN were evaluated at centres in Buenos Aires, Bahía Blanca, Mendoza, and La Pampa between 1/1/00 and 12/31/01. Clinical examination, thyroid ultrasound scan (US), TSH, TPOAb and fine needle aspirations (FNA) were performed. Statistics: Pearson Correlation, X2 & Fisher Tests. Results: Age (X ± SD) 46 ± 14ys: 93.1 % were women. Previous history of neck radiation & familial thyroid disease were found in 1.6 and 29.9 % respectively. Clinical findings: dysphagia: 7.9 %; dysphonia: 3.5%; nodule growth: 19.2 %; hard consistence: 24.7 %; fixation to adjacent structure: 1.5 % and lymphadenopathies (ADP): 3 %. Biochemical findings: TSH was normal in 81.2 % & TPOAb+ in 30.3 %. US features: solid: 53.1 %; hypoechoic: 63.8 %; microcalcifications: 10.3 %; incomplete halo: 15 %; more than 1 nodule: 30.5 %; thyroid heterogeneity: 60.2 % and ADP: 3.8 %. Cytology: Only 1 FNA was needed in 86.8%. Unsatisfactory (excluding cysts): 3.2 %; benign: 77.2%; suspicious: 12.6 % and cancer: 7 % (42 papillary, 2 medullary and 3 non specified). A significant correlation (p<0.02) was established between malignant nodules and rapid growth, hard, fixed, solid nodule, incomplete halo and ADP, though these parameters were more frequent (in absolute number) in benign nodules. Surgery was mainly indicated based on FNA results. Histological diagnosis of 96 patients who underwent surgery showed 51 carcinomas, of which only 2 were cytologically benign and 31 adenomas. Conclusion: Palpable single nodules were more frequent in middle aged euthyroid women. One third had familial thyroid pathology, similar to the presence of TPOAb. On US, nodules were predominantly solid, hypoechoic, single with heterogeneous thyroid gland. FNA was predominantly benign. Rapid growth, hard, fixed, solid nodule, incomplete halo and ADP were associated with malignancy, but benignity was more common. In most of the patients surgery was recommended based on cytological findings. Our results are similar to those reported in other geographic areas.

Comparative efficacy and side effects of the treatment of euthyroid goiter with levo-thyroxine or triiodothyroacetic acid.

Euthyroid goiter is usually treated with TSH-inhibitory doses of levo-T(4) (L-T(4)). Because triiodothyroacetic acid (TRIAC) decreases TSH levels, the following study was perfomed: 36 euthyroid goitrous female patients (no cancer or chronic thyroiditis) were randomized to TRIAC (19.6 micro g/kg) (n = 19) or L-T4 (1.7 microg/kg) (n = 17) treatment during 11 months. Goiter volume; lumbar and femoral bone mineral density; serum osteocalcin; deoxypyridinoline; TSH; free T(4); total, high-density lipoprotein, and low-density lipoprotein cholesterol; and triglycerides were measured before and after the study period. Student's t test and chi(2) analysis were performed. TSH values (microunits per milliliter) in the TRIAC and L-T(4) groups were: 1.91 +/- 0.6 (basal) and 0.180 +/- 0.1 (after) and 2.1 +/- 2.5 (basal) and 0.180 +/- 0.3 (after), respectively. Thyroid volume decreased 37.9 +/- 35.4% in the TRIAC patients and 14.5 +/- 39.5% in the L-T(4) group (P = 0.069). Forty-two percent of the goiters with TRIAC reduced more than 50% their initial volume vs. 17.7% with L-T(4) (P = 0.15). With TRIAC, patients experienced fewer side effects. No differences in the changes of bone mineral density, serum deoxypyridinoline, osteocalcin, or the lipid profile were observed between both groups. The present results show that TRIAC is more effective than L-T(4) in the reduction of goiter size, with comparable effects on peripheral parameters.

Characterization of sex hormone-binding globulin isoforms in hypothyroid women.

Liver sex hormone-binding globulin (SHBG) biosynthesis is regulated by triiodothyronine (T3). This regulation is responsible for increased serum SHBG concentrations in hyperthyroid states. However, in hypothyroidism, normal SHBG levels are frequently found. To understand this we have characterized circulating SHBG isoforms according to their sialic acid content, which determines its half-life, in euthyroid and hypothyroid women. Six euthyroid (aged 56 +/- 8 years) and five hypothyroid women (51 +/- 13 years) were studied. Their body mass index (BMI) range was 20-25. Hypothyroidism diagnosis was based on clinical findings, elevated basal thyrotropin (TSH) and decreased T3 and thyroxine (T4) values. Total SHBG was measured by radioimmunoassay (RIA) and SHBG isoforms were isolated using preparative isoelectrofocusing. For comparisons, two-tailed t test was applied. No statistical difference was found between the total SHBG levels of hypothyroid and euthyroid postmenopausal women. Three groups of SHBG isoforms were isolated in the euthyroid group: S(I): pl: 5.0-5.2: 20% +/- 4%, S(II) : pl 5.2-5.4: 50% +/- 3% and S(III): pl 5.4-5.6: 29% +/- 4%. In hypothyroid patients, although the three groups of isoforms were isolated in the same pH range, S(I) and S(II) proportions were different (p < 0.001) when compared to normal women: S(I): 34% +/- 4%, S(II): 33% +/- 9.9% and S(III): 29% +/- 5.7%. These results show that hypothyroid patients have a higher proportion of more acidic SHBG isoforms. This variation may explain the normal levels of serum SHBG observed in hypothyroidism.

Variations of sex hormone-binding globulin in thyroid dysfunction.

With the aim of understanding the variations of the levels of sex hormone-binding globulin (SHBG) in thyroid dysfunction, we studied the influence of factors that also modify SHBG, such as menopausal status, age, and body mass index (BMI) in women with hypothyroidism and hyperthyroidism, both overt and subclinical. Statistical analysis was performed by means of analysis of variance (ANOVA), stepwise multiple regression, and partial correlation. The ANOVA showed a significant statistical difference among the means of SHBG of all groups (p<0.01). The difference was due to the group that included hyperthyroid women. Multiple regression analysis showed that the main factors influencing SHBG were BMI and age, except for the hyperthyroid group, where the most important independent variables were triiodothyronine (T3) and thyroxine (T4). Partial correlation controlling the effect of BMI and age showed no association between SHBG and the other variables in all groups except for the subclinical hyperthyroid and hyperthyroid, where we found a significant association between SHBG and T4 and T3. The premenopausal or postmenopausal status did not modify SHBG levels. When the patients are taken as a whole, BMI, age, T4, and T3 all have an association with SHBG levels according to the multiple regression analysis.

Studies of allelic loss in thyroid tumors reveal major differences in chromosomal instability between papillary and follicular carcinomas.

Loss of heterozygosity (LOH) studies have been used to identify sites harboring tumor suppressor genes involved in tumor initiation or progression. Previous reports have suggested that regions within chromosomes 3p, 11q, 2p, 2q, 10q, and 1p may be frequently deleted in human follicular thyroid cell tumors. We have extended the analysis of these and other selected regions to 65 paired thyroid tumor tissues. Twenty-four were follicular adenomas, 30 were papillary carcinomas, 10 were follicular carcinomas, and 1 was an anaplastic carcinoma. Sixty percent of the follicular carcinomas, 33% of the follicular adenomas, and 23% of the papillary carcinomas presented LOH at least at 1 site. Fifty percent of the follicular carcinomas showed 2 or more chromosome arms affected by deletions, whereas just 1 of the 24 follicular adenomas and none of the papillary carcinomas presented this feature. However, none of the specific loci examined had a rate of LOH greater than 33%, even in follicular carcinomas. This prompted us to place our findings into a broader context, and we, therefore, performed a meta analysis of all published studies of LOH in follicular thyroid neoplasms. There was a phenotype dependency in the overall rate of LOH, with no specific region displaying a particularly high prevalence. Most notably, by contrast to follicular carcinomas, papillary carcinomas had exceedingly low rates of LOH. Thus, there is a sharp distinction between the two major forms of differentiated thyroid cancer in their tendency to lose genetic material. This probably results from a fundamental difference in mechanisms controlling chromosomal stability in these two forms of cancers that in all likelihood has implications for tumor behavior and prognosis.